Obesity and diabetes are more common in African-Americans than whites. Because free fatty acids (FFA) participate in the development of these conditions, studying race differences in the regulation of FFA and glucose by insulin is essential. Background: Quantitative evaluation of insulin regulation on plasma glucose and free fatty acid (FFA) in response to external glucose challenge is clinically important to assess the development of insulin resistance. Mathematical minimal models (MMs) based on insulin modified frequently-sampled intravenous glucose tolerance tests (IM-FSIGT) are widely applied to ascertain an insulin sensitivity index. However, the action of insulin on FFA kinetics is not considered in most MMs. Neither glucose clamps nor IM-FSIGT are normal physiological conditions so it is important to quantify insulin modulation of glucose and FFA metabolism in postprandial state. Methods: A new MM is developed to simulate the insulin modulation of plasma glucose and FFA, combining IM-FSIGT with a mixed meal tolerance test (MT). A novel functional form for the appearance rate (Ra) of glucose or FFA in the MT is developed. Model results are compared with two other models for data obtained from 28 non-diabetic women (13 African American, 15 white). Results: The new functional form for Ra of glucose is a good empirical approximation to the experimental Ra. When both glucose and FFA are included in FSIGT and MT, the new model is preferred using the Bayes Information Criterion (BIC). Conclusions: Model simulations show that the new MM allows consistent application to both IM-FSIGT and MT data, balancing model complexity and data fitting. While the appearance of glucose in the circulation has an important effect on FFA kinetics in MT, the rate of appearance of FFA can be neglected. We have also worked with Dr. Sumner's group in analyzing Vitamin D levels in connection with bone density and thyroid hormone.

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9
Fiscal Year
2015
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Name
U.S. National Inst Diabetes/Digst/Kidney
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